Baicalin attenuates morphine tolerance through suppressing spinal microglia activation in mice

The aim of the present study was to investigate the effects and possible mechanisms of baicalin on morphine induced microglia activation and morphine tolerance. Cytokine IL-1β and TNF-α expression were analyzed by reverse transcription polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA), and the level of p38 MAP kinase phosphorylation and IBA-1 expression was determined by Western blot, the antinociception and morphine tolerance were assessed in mice using hot-plate test. Results showed that baicalin(1, 10, 100 μmol/L)inhibited morphine induced up-regulated levels of IL-1β, TNF-α in BV-2 microglia cells in a dose-dependent manner; and that 100 μmol/L baicalin significantly inhibited the level of p38MAP kinase phosphorylation induced by morphine in BV2 microglia cells. Intrathecal(it. )injection of baicalin(20, 40, 60 μg)attenuated the development of chronic morphine tolerance in a dose-dependent manner. Baicalin(60 μg)mimicked the role of minocycline and significantly suppressed the level of p38MAP kinase phosphorylation induced bychronic morphine treatment and IBA-1expression in mice spinal cord. In conclusion, baicalin suppresses morphine-induced microglia activation through suppressing p38MAPK signaling, resulting in significant attenuation of morphine antinociceptive tolerance.